NCT05007977

Effect of ZT-01 on Glucagon During Hypoglycemia in Type 1 Diabetes Mellitus

Pharmacodynamic Evaluation of ZT-01 in a Stepped Hypoglycemic Clamp Model in Subjects With Type 1 Diabetes Mellitus

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Zucara Therapeutics Inc. · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether ZT-01 increases the glucagon response to hypoglycemia in type 1 diabetes (T1D). ZT-01 is a specific somatostatin (SST) type 2 receptor antagonist hypothesized to increase the counterregulatory glucagon release during hypoglycemia, which is impaired in diabetes, and may thus reduce the occurrence of hypoglycemia. Approximately 25 participants with well-controlled type 1 diabetes will be recruited to a crossover study and be randomized to the order in which they receive a single administration of placebo, low dose and high dose ZT-01 during three euglycemic-hypoglycemic clamps 2 to 6 weeks apart, with a follow-up visit approximately 1 week after the final clamp. Participants will stay overnight in the clinic before each clamp, and their plasma glucose (PG) will be kept at euglycemic levels with IV insulin and dextrose as needed. The following morning, the clamp will begin and the subject's PG will be kept at 5.5 mmol/L (euglycemia) with variable IV insulin (and dextrose as needed). Study treatment will be administered during this euglycemic period, and then insulin will be increased so that PG falls to a plateau of mild hypoglycemia, and then increased further to clinically significant hypoglycemia. Release of glucagon and other counterregulatory hormones will be measured, and a symptom score will be completed, during euglycemia before and following study treatment, and during each level of hypoglycemia. Following the clamp, the participant's blood glucose will be returned to normal levels prior to leaving the clinic.

Conditions

• Type 1 Diabetes
• Hypoglycemia

Interventions

Type	Name	Description
DRUG	ZT-01 low dose	Single subcutaneous (SC) injection of ZT-01 3 mg during hypoglycemic clamp
DRUG	ZT-01 high dose	Single SC injection of ZT-01 20 mg during hypoglycemic clamp
DRUG	Placebo	Single SC injection of placebo during hypoglycemic clamp

Timeline

• Start date: 2021-07-08
• Primary completion: 2022-04-12
• Completion: 2022-04-18
• First posted: 2021-08-17
• Last updated: 2023-07-12

Locations

1 site across 1 country: Canada